Pathogenesis Infarction Classification Notes

Infarction

Infarction is the process of tissue necrosis, usually coagulative type, resulting from ischaemia; the localised area of necrosis so developed is called an infarct. However, in infarcts of the brain, necrosis is a liquefaction type.

Read And Learn More: General Pathology Notes

Etiology:

All the causes of ischaemia may produce infarction. According to the levels of vasculature affected, these causes are as under:

Causes in the heart: Inadequate cardiac output resulting from heart block, ventricular arrest and fibrillation from various causes may cause variable degree of hypoxic injury to the brain as under:

• If the arrest continues for 15 seconds, consciousness is lost.
• If the condition lasts for more than 4 minutes, irreversible ischaemic damage to the brain occurs.
• If it is prolonged for more than 8 minutes, death is inevitable.

 Causes in the arteries:  The commonest and most important causes of ischaemia are due to obstruction in arterial blood supply as under:

• Luminal occlusion of artery (intraluminal):
  • Thrombosis
  • Embolism
• Causes in the arterial walls (intramural):
  • Vasospasm ( for example, In Raynaud’s disease)
  • Hypothermia, ergotism
  • Arteriosclerosis
  • Polyarteritis nodosa
  • Thromboangiitis obliterans (Buerger’s disease)
  • Severed vessel wall
• Outside pressure on an artery (extramural):
  • Ligature
  • Tourniquet
  • Tight plaster, bandages
  • Torsion

Causes in the veins:

Blockage of venous drainage may lead to engorgement and obstruction to arterial blood supply resulting in ischaemia.

The examples include the following:

• Luminal occlusion of vein (intraluminal):
  • Thrombosis of mesenteric veins
  • Cavernous sinus thrombosis
• Causes in the vessel wall of vein (intramural):
  • Varicose veins of the legs
• Outside pressure on vein (extramural):
  • Strangulated hernia
  • Intussusception
  • Volvulus

Causes in the microcirculation:

Ischaemia may result from occlusion of arterioles, capillaries and venules. The causes are as under:

• Luminal occlusion in the microvasculature (intraluminal):
  • By red cells for example, In sickle cell anaemia, red cells parasitised by malaria, acquired haemolytic
    anaemia, sludging of the blood.
  • By white cells for example, In chronic myeloid leukaemia
  • By fibrin for example, Defibrination syndrome
  • By precipitated cryoglobulins
  • By fat embolism
  • In decompression sickness.

Causes in the microvasculature wall (intramural):

• Vasculitis for example, In polyarteritis nodosa, Henoch-Schönleinpurpura, Arthus reaction, septicaemia.
• Frost-bite injuring the wall of small blood vessels.

Outside pressure on microvasculature (extramural):

• Bedsores. However, there are a few other noteworthy features in infarction:
• Most commonly, infarcts are caused by interruption in arterial blood supply, called ischaemic necrosis.
• Less commonly, venous obstruction can produce infarcts termed stagnant hypoxia.
• Generally, sudden, complete, and continuous occlusion ( for example, Thrombosis or embolism) produces infarcts.
• Infarcts may be produced by non-occlusive circulatory insufficiency as well for example, Incomplete
  atherosclerotic narrowing of coronary arteries may produce myocardial infarction due to acute coronary insufficiency.

Factors Determining Severity of Ischaemic Injury:

The extent of damage produced by ischaemia due to occlusion of arterial or venous blood vessels depends upon a number of factors as under:

1. Anatomic pattern:

The extent of injury by ischaemia depends upon the anatomic pattern of the arterial blood supply of the organ or tissue affected. There are 4 different patterns of arterial blood supply:

• Single arterial supply without anastomosis:  Some organs receive blood supply from arteries which do not have significant anastomosis and are thus functional end-arteries. Occlusion of such vessels invariably results in ischaemic necrosis.
• For example:
  • Central artery of the retina
  • Interlobular arteries of the kidneys.
• Single arterial supply with rich anastomosis:  Arterial supply to some organs has rich intraarterial anastomoses so that blockage of one vessel can re-establish blood supply bypassing the blocked arterial branch, and hence infarction is less common in such circumstances.
• For example:
  • Superior mesenteric artery supplying blood to the small intestine.
  • Inferior mesenteric artery supplying blood to distal colon.
  • Arterial supply to the stomach by 3 separate vessels derived from the coeliac axis.
  • Interarterial anastomoses in the 3 main trunks of the coronary arterial system.
• Parallel arterial supply Blood:  supply to some organs and tissues is such that vitality of the tissue is maintained by an alternative blood supply in case of occlusion of one.
• For example:
  • Blood supply to the brain in the region of circle of Willis.
  • Arterial supply to the forearm by radial and ulnar arteries.
• Double blood supply:  The effect of occlusion of one set of vessels is modified if an organ has dual blood supply.
• For example:
  • Lungs are perfused by bronchial circulation as well as by pulmonary arterial branches.
  • Liver is supplied by both portal circulation and hepatic arterial flow.

However, collateral circulation is of little value if the vessels are severely affected with spasms, atheroma or any other such condition.

2. General and cardiovascular status: The general status of an individual as regards cardiovascular function is an important determinant to assess the effect of ischaemia.

Some of the factors which render the tissues more vulnerable to the effects of ischaemia are as under:

• Anaemias (sickle cell anaemia, in particular)
• Lowered oxygenation of blood (hypoxaemia)
• Senility with marked coronary atherosclerosis
• Cardiac failure
• Blood loss
• Shock.

3. Type of tissue affected: Vulnerability of the tissue of the body to the effect of ischaemia is variable. Mesenchymal tissues are quite resistant to the effect of ischaemia as compared to

• Brain (cerebral cortical neurons, in particular).
• Heart (myocardial cells).
• Kidney (especially epithelial cells of proximal convoluted tubules).

4. Rapidity of development: Sudden vascular obstruction results in more severe effects of ischaemia than if it is gradual since there is less time for collaterals to develop.

5. Degree of vascular occlusion: Complete vascular obstruction results in more severe ischaemic injury than partial occlusion.

Pathogenesis:

The sequence of changes in infarction is as under:

• Localised hyperaemia occurs immediately after obstruction of the blood supply.
• Within a few hours, the affected part becomes swollen due to oedema and haemorrhage.
• The amount of haemorrhage is variable, being more marked in the lungs and spleen, and less extensive in the kidneys and heart.
• Cellular changes such as cloudy swelling and degeneration appear early (reversible cell injury), while cell death (irreversible cell injury or necrosis) occurs in 12-48 hours.
• There is progressive proteolysis of the necrotic tissue and there is lysis of the red cells.
• An acute inflammatory reaction and hyperaemia appear at the same time in the surrounding tissues in response to products of proteolysis.
• Blood pigments, haematoidin and haemosiderin, liberated by lysis of RBCs are deposited in the infarct. At this stage, most infarcts become pale-grey due to loss of red cells.
• Following this, there is progressive ingrowth of granulation tissue from the margin of the infarct so that eventually the infarct is replaced by a fibrous scar. Dystrophic calcification may occur sometimes.

Types of Infarcts:

Infarcts are classified depending upon different features:

• According to their colour:
  • Pale or anaemic: Due to arterial occlusion and are seen in compact organs for example, In the kidneys, heart, and spleen.
  • Red or haemorrhagic: Seen in soft loose tissues and are caused either by pulmonary arterial obstruction ( for example, In the lungs) or by arterial or venous occlusion ( for example, In the intestines).

• According to their age:
  • Recent or fresh
  • Old or healed
• According to presence or absence of infection:
  • Bland, when free of bacterial contamination
  • Septic, when infected.

Morphologic Features of Infarcts of Different Organs:

A few representative examples of infarction of some organs (lungs, kidney, liver and spleen) are discussed below.

Myocardial infarction , cerebral infarction and infarction of the small intestines are covered in detail in the respective chapters of Systemic Pathology. Shows the organs commonly affected by infarction while summing up the gross appearance and the usual outcome of the common types of infarction.

Infarct Lung:

Embolism of the pulmonary arteries may produce pulmonary infarction, though not always. This is because lungs receive blood supply from bronchial arteries as well, and thus occlusion of pulmonary artery ordinarily does not produce infarcts.

However, it may occur in patients who have inadequate circulation such as in chronic lung diseases and congestive heart failure.

• Grossly: Pulmonary infarcts are classically wedge-shaped with base on the pleura, haemorrhagic, variable in size, and most often in the lower lobes . Fibrinous pleuritis usually covers the area of the infarct. Cut surface is dark purple and may show the blocked vessel near the apex of the infarcted area. Old organised and healed pulmonary infarcts appear as retracted fibrous scars.
• Microscopically: The characteristic histologic feature is coagulative necrosis of the alveolar walls. Initially, there is infiltration by neutrophils and intense alveolar capillary congestion, but later their place is taken by haemosiderin, phagocytes and granulation tissue

Infarcts of commonly affected organs

Infarct Kidney:

Renal infarction is common, found in up to 5% of autopsies. The majority of them are caused by thromboembolic, most commonly originating from the heart such as in mural thrombi in the left atrium, myocardial infarction, vegetative endocarditis and aortic aneurysm.

Less commonly, renal infarcts may occur due to advanced renal artery atherosclerosis, arteritis and sickle cell anaemia.

• Grossly: Renal infarcts are often multiple and may be bilateral. Characteristically, they are pale or anaemic and wedge-shaped with base resting under the capsule and apex pointing towards the medulla.
• Generally: A narrow rim of preserved renal tissue under the capsule is spared because it draws its blood supply from the capsular vessels. Cut surface of renal infarct in the first 2 to 3 days is red and congested but by 4th day the centre becomes pale yellow. At the end of one week, the infarct is typically anaemic and depressed below the surface of the kidney
• Microscopically: The affected area shows characteristic coagulative necrosis of renal parenchyma i.e. there are ghosts of renal tubules and glomeruli without intact nuclei and cytoplasmic content. The margin of the infarct shows inflammatory reaction—initially acute but later macrophages and fibrous tissue predominate.

Infarct Spleen:

Spleen is one of the common sites for infarction. Splenic infarction results from occlusion of the splenic artery or its branches.

Occlusion is caused most commonly by thromboembolic arising in the heart ( for example, In mural thrombi in the left atrium, vegetative endocarditis, myocardial infarction), and less frequently by obstruction of microcirculation ( for example, I n myeloproliferative diseases, sickle cell anaemia, arteritis, Hodgkin’s disease, bacterial infections).

• Grossly: Splenic infarcts are often multiple. They are characteristically pale or anaemic and wedge-shaped with their base at the periphery and apex pointing towards the hilum.
• Microscopically: The features are similar to those found in anaemic infarcts in the kidney. Coagulative necrosis and inflammatory reaction are seen. Later, the necrotic tissue is replaced by a shrunken fibrous scar.

Infarct Liver:

Just as in lungs, infarcts in the liver are uncommon due to dual blood supply —from the portal vein and from the hepatic artery. Obstruction of the portal vein is usually secondary to other diseases such as hepatic cirrhosis, intravenous invasion of primary carcinoma of the liver, carcinoma of the pancreas and pylephlebitis.

Occlusion of portal vein or its branches generally does not produce ischaemic infarction but instead reduced blood supply to hepatic parenchyma causes non-ischaemic infarct called infarct of Zahn.

Obstruction of the hepatic artery or its branches, on the other hand, caused by arteritis, arteriosclerosis, bland or septic emboli, results in ischaemic infarcts of the liver.

• Grossly: Ischaemic infarcts of the liver are usually anaemic but sometimes may be haemorrhagic due to stuffing of the site by blood from the portal vein. Infarcts of Zahn (nonischemic infarcts) produce sharply defined red-blue area in liver parenchyma.
• Microscopically: Ischaemic infarcts show characteristics of pale or anaemic infarcts as in the kidney or spleen. Infarcts of Zahn occur due to reduced portal blood flow over a long uration result in chronic atrophy of hepatocytes and dilatation of sinusoids

Infarction:

Infarction is the process of tissue necrosis, usually a coagulative type, resulting from ischaemia; the localised area of necrosis so developed is called an infarct. However, in the brain, it is liquefactive necrosis.

• Causes of ischaemia may lie in the heart, arteries, veins and microcirculation.
• The severity of ischaemic injury depends upon the anatomic pattern of blood supply, general and cardiovascular status, type of tissue affected, and speed of development of ischaemia.
• Infarcts may be pale or haemorrhagic, bland or infected, recent or old healed.
• Some of the common locations of infarcts are: the brain, heart, kidneys, spleen, small intestines, and lower extremities.
• The hallmark microscopic feature of infarcts is coagulative necrosis in which outlines of cells are retained but their details are lost, and there is an inflammatory reaction by the host. Infarction of the lungs and liver is less frequent due to dual blood supply to both these organs